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PubMed1984

The current status of human monkeypox: memorandum from a WHO meeting.

In spite of a recent increase in the number of reported cases, human monkeypox remains a rare sporadic zoonotic disease with limited capacity to spread between humans. As such, the disease does not at present require specific public health measures. However, much of the population in the enzootic region, especially in the 5-14-year age group, still retains some immunity as a result of vaccination against smallpox. Continuation of surveillance activities on the same scale as at present until 1989 should provide a clear indication of the extent to which human monkeypox may be considered a public health problem, either generally or in particular localities. Such surveillance should also provide a definitive clinical and epidemiological picture of this newly discovered disease. Further research on its ecology and epidemiology will be facilitated by the development of a simple, specific and sensitive serological test for monkeypox virus-specific antibodies.

Adolescent↗

PubMed1972

Isolation and properties of the causal agent of a new variola-like disease (monkeypox) in man.

The causal agent of a case of disease in man occurring in the Democratic Republic of the Congo with a similar clinical picture to smallpox was isolated and studied. The agent was identified as monkeypox virus. A comparative study of the isolated strain (Congo-8) and of viruses isolated from similar cases of illness in Liberia (Liberia-1 and Liberia-2 strains) and Sierra Leone (V-70 1 266 strain) showed that they were identical. A number of local species of monkeys and apes were examined serologically in the Congo region to determine the probability of human infection with monkeypox virus. It was confirmed that the animals had had contact with an agent of the poxvirus group. In 2 of the 7 sera examined, antibodies of the variola-vaccinia group of poxviruses were discovered (virus-neutralizing antibodies, precipitins, and antihaemagglutinins). In a chimpanzee, antihaemagglutinins were found in a titre of 1: 1 280, and in the same animal a variola-like virus was isolated from the kidneys. In the course of the investigation, it was shown conclusively that monkeypox virus and the strains under investigation could be distinguished from o dinary variola and vaccinia viruses on the basis of their behaviour in pig embryo kidney continuous cell line culture.

Animals↗

PubMed1972

Studies on monkeypox virus.

The growth characteristics, including ceiling temperatures for growth, of three strains of monkeypox virus were studied on chick chorioallantoic membrane, growth and plaque formation were studied in RK13 cells, and growth was studied in rabbit dermis. The three strains could not be distinguished by these tests but could be differentiated from variola, vaccinia, and cowpox viruses. Haemagglutination-inhibition tests with homologous and heterologous antisera also showed that the monkeypox strains were indistinguishable, although they could be differentiated from vaccinia and cowpox, but not from variola, viruses. Similar results were obtained in neutralization tests. It is suggested that the monkeypox strains constitute a homogeneous poxvirus entity. The strains can be differentiated from other poxviruses by their cultural characteristics but serologically they are more closely related to variola than to vaccinia or cowpox viruses.

Animals↗

PubMed1968

Smallpox and monkeypox in non-human primates.

In considering global eradication of smallpox the absence of an animal reservoir is important. Present knowledge of experimental infection of non-human primates with variola virus and of a related virus infection in monkeys, termed monkeypox, is examined.From the literature review and the results of a survey of captive monkeys in 26 major biological institutions it is concluded that outbreaks of supposed smallpox and monkeypox are not frequent and that man may be comparatively insusceptible to monkeypox. A natural reservoir of smallpox in non-human primates is thought to be unlikely although further studies are warranted since the survey reveals that certain species of monkeys can be infected with smallpox and that infected monkeys can transmit infection to others.

Animals↗

PubMed2005

Virulence differences between monkeypox virus isolates from West Africa and the Congo basin.

Studies indicate that West African and Congo basin isolates of monkeypox virus (MPXV) are genetically distinct. Here, we show Congo basin MPXV-ZAI-V79 is more virulent for cynomolgus monkeys as compared to presumed West African MPXV-COP-58. This finding may explain the lack of case-fatalities in the U.S. 2003 monkeypox outbreak, which was caused by a West African virus. Virulence differences between West African and Congo basin MPXV are further supported by epidemiological analyses that observed a similar prevalence of antibodies in non-vaccinated humans in both regions, while >90% of reported cases occurred in the Congo basin, and no fatal cases were observed outside of this region. To determine the basis for this difference in virulence, we sequenced the genomes of one human West African isolate, and two presumed West African isolates and compared the sequences to Congo basin MPXV-ZAI-96-I-16. The analysis identified D10L, D14L, B10R, B14R, and B19R as possible virulence genes, with D14L (ortholog of vaccinia complement protein) as a leading candidate.

Africa, Western↗

PubMed2005

Antiviral treatment is more effective than smallpox vaccination upon lethal monkeypox virus infection.

There is concern that variola virus, the aetiological agent of smallpox, may be used as a biological weapon. For this reason several countries are now stockpiling (vaccinia virus-based) smallpox vaccine. Although the preventive use of smallpox vaccination has been well documented, little is known about its efficacy when used after exposure to the virus. Here we compare the effectiveness of (1) post-exposure smallpox vaccination and (2) antiviral treatment with either cidofovir (also called HPMPC or Vistide) or with a related acyclic nucleoside phosphonate analogue (HPMPO-DAPy) after lethal intratracheal infection of cynomolgus monkeys (Macaca fascicularis) with monkeypox virus (MPXV). MPXV causes a disease similar to human smallpox and this animal model can be used to measure differences in the protective efficacies of classical and new-generation candidate smallpox vaccines. We show that initiation of antiviral treatment 24 h after lethal intratracheal MPXV infection, using either of the antiviral agents and applying various systemic treatment regimens, resulted in significantly reduced mortality and reduced numbers of cutaneous monkeypox lesions. In contrast, when monkeys were vaccinated 24 h after MPXV infection, using a standard human dose of a currently recommended smallpox vaccine (Elstree-RIVM), no significant reduction in mortality was observed. When antiviral therapy was terminated 13 days after infection, all surviving animals had virus-specific serum antibodies and antiviral T lymphocytes. These data show that adequate preparedness for a biological threat involving smallpox should include the possibility of treating exposed individuals with antiviral compounds such as cidofovir or other selective anti-poxvirus drugs.

Animals↗

PubMed2005

Smallpox vaccine-induced antibodies are necessary and sufficient for protection against monkeypox virus.

Vaccination with live vaccinia virus affords long-lasting protection against variola virus, the agent of smallpox. Its mode of protection in humans, however, has not been clearly defined. Here we report that vaccinia-specific B-cell responses are essential for protection of macaques from monkeypox virus, a variola virus ortholog. Antibody-mediated depletion of B cells, but not CD4+ or CD8+ T cells, abrogated vaccine-induced protection from a lethal intravenous challenge with monkeypox virus. In addition, passive transfer of human vaccinia-neutralizing antibodies protected nonimmunized macaques from severe disease. Thus, vaccines able to induce long-lasting protective antibody responses may constitute realistic alternatives to the currently available smallpox vaccine (Dryvax).

Animals↗

PubMed2005

Modified vaccinia virus Ankara protects macaques against respiratory challenge with monkeypox virus.

The use of classical smallpox vaccines based on vaccinia virus (VV) is associated with severe complications in both naive and immune individuals. Modified vaccinia virus Ankara (MVA), a highly attenuated replication-deficient strain of VV, has been proven to be safe in humans and immunocompromised animals, and its efficacy against smallpox is currently being addressed. Here we directly compare the efficacies of MVA alone and in combination with classical VV-based vaccines in a cynomolgus macaque monkeypox model. The MVA-based smallpox vaccine protected macaques against a lethal respiratory challenge with monkeypox virus and is therefore an important candidate for the protection of humans against smallpox.

Animals↗

PubMed1977

The virion and soluble antigen proteins of variola, monkeypox, and vaccinia viruses.

The structural proteins in purified preparations of variola, monkeypox, and vaccinia viruses were separated and compared by using a high resolution SDS-polyacrylamide gel electrophoresis system. About 30 proteins were resolved for each virus by autoradiography of longitudinally-sliced gel rods. Although the autoradioelectropherograms of each virus were similar, it was possible to differentiate them by their unique protein pattern in the 30,000 to 40,000 molecular weight region of the gels. A single virion glycoprotein (mol. wt. = 38 X 10(3)) and a virion phosphoprotein (mol. wt. = 12 X 10(3)) were associated with each of the virus preparations. Cross-absorbed monospecific immune sera against variola, monkeypox, and vaccinia virus-infected cells were used in immunodiffusion tests to precipitate radiolabeled, homologous, soluble antigen proteins. The predominant antigen protein associated with each immunospecific precipitate had a molecular weight of approximately 73,000.

Antigens, Viral↗

PubMed1990

Nucleotide sequence comparison of homologous genomic regions from variola, monkeypox, and vaccinia viruses.

The nucleotide sequences of homologous regions from the genomes of variola major strain Harvey, variola minor strains Butler and Garcia, and monkeypox strain Denmark were determined. The nucleotide sequences were compared to the homologous region in vaccinia virus which contains part of one of the genes involved in determining host range. Two major differences were detected; these corresponded to a deletion in the promoter region and the presence of a premature stop codon. It was concluded that this region of the genome may not be actively expressed in either variola- or monkeypox-virus-infected cells. It was also concluded that diagnostic nucleic acid hybridisation probes for differentiating between these members of the Orthopoxviridae may be difficult to identify.

Chromosome Deletion↗

PubMed1985

The histopathology and electron microscopy of a human monkeypox lesion.

The histological and electron microscopic findings from a solitary cutaneous monkeypox lesion taken post mortem from a child who died after a five-day illness are reported. This child is 44th in the WHO register of monkeypox cases. The lesion was at the papulonecrotic stage, with early evidence of vesiculation and minimal evidence of pustulation. Necrosis affected the stratum basale, the related basement membrane and adjacent areas of the dermal papillae at the centre of the lesion. Cell necrosis affected the next two or three layers of stratum spinosum above the destroyed stratum basale. Lateral to this zone, marked hyperplasia and intracellular oedema of the stratum spinosum constituted the papule and produced spindle-cell features. In the middle layer of the stratum spinosum, above the necrotic focus, there were minute vesicles and between these were occasional multinuclear giant cells. Bodies similar to Guarnieri bodies (GB) were present in the cytoplasm of sweat duct-lining cells in the epidermis and upper corium. Very scanty similar bodies were evident elsewhere in the papular epidermis but were difficult to distinguish from debris. Granules in the lesion with the same size as mature virions (elementary bodies) have been assessed not to be these because similar granules are present in the normal epidermis. Changes in the dermis apart from those mentioned above were minimal oedema, very mild perivascular infiltration by round cells and an occasional eosinophil. Electron microscopy showed abundant immature and mature orthopoxvirus particles in the cytoplasms of infected epidermal cells. A limited range of histochemical tests is detailed. In general, the features are indistinguishable from the papulonecrotic stage of smallpox (variola) and from tanapox as recorded in man.

Child, Preschool↗

PubMed1984

Nucleotide sequence of the thymidine kinase gene region of monkeypox and variola viruses.

Among the orthopoxviruses variola virus induces in cells a characteristic thymidine kinase (TK) activity that can be feedback inhibited in reactions with thymidine triphosphate. Northern blot analyses of variola and monkeypox virus-infected cell extracts showed RNAs of the same molecular weight as the major (590-base) and minor (2380-base) TK transcripts described for vaccinia virus. The nucleotide sequences of 1275 bp in the TK gene region of variola and monkeypox viruses have been determined. When these sequences were compared with such sequences reported for vaccinia virus, differences were observed at 41 nucleotide positions. Examination of the putative encoded TK polypeptide for the three viruses revealed variation at eight amino acid positions. Two major differences in the amino acid composition of the variola virus TK were identified that might play a role in alteration of its kinetic properties.

Amniotic Fluid↗

PubMed2001

Human monkeypox and smallpox viruses: genomic comparison.

Monkeypox virus (MPV) causes a human disease which resembles smallpox but with a lower person-to-person transmission rate. To determine the genetic relationship between the orthopoxviruses causing these two diseases, we sequenced the 197-kb genome of MPV isolated from a patient during a large human monkeypox outbreak in Zaire in 1996. The nucleotide sequence within the central region of the MPV genome, which encodes essential enzymes and structural proteins, was 96.3% identical with that of variola (smallpox) virus (VAR). In contrast, there were considerable differences between MPV and VAR in the regions encoding virulence and host-range factors near the ends of the genome. Our data indicate that MPV is not the direct ancestor of VAR and is unlikely to naturally acquire all properties of VAR.

Amino Acid Sequence↗

PubMed2004

Monkeypox: a review of the history and emergence in the Western hemisphere.

A mysterious disease was reported on May 24, 2003, when the Wisconsin Division of Public Health (DPH) received notice of a 3-year-old girl who had been hospitalized in central Wisconsin with cellulites and fever after being bitten by a prairie dog on May 13. The laboratory isolated a gram-negative bacillus, raising concerns that it might be tularemia or plague; ultimately, it was identified as an acinetobacter species and was considered to be a contaminant. Because no other such cases were reported at the time, the case was thought to be merely an isolated event. However, within two weeks, on June 2, 2003, evidence of a much wider scenario began to emerge. On that date, the Wisconsin DPH received notice from the Marshfield Laboratory that the mother of the first patient had become ill on May 26 and that electron-microscopic evidence of a poxvirus was found in a skin lesion. On that same day, another report, this time from the Milwaukee Health Department, of a strange illness was received at the DPH and described the case of a meat inspector who resided in southeastern Wisconsin and also was a distributor of exotic animals. By July 30, 2003, 72 confirmed or suspected cases of monkeypox had been reported in Wisconsin, Illinois, and Indiana and represented a large outbreak. The peak in the onset of illness occurred between May 29 and June 9, 2003, and no further cases of illness have been reported in humans since June 22, 2003. Traceback investigations from the child and other patients followed the route of introduction of monkeypox into Wisconsin to a distributor in Illinois, who had received a shipment of exotic animals imported into the United States through Texas from Ghana, West Africa.

Adult↗

PubMed1987

Human monkeypox: clinical features of 282 patients.

We present the clinical features and course of 282 patients with human monkeypox in Zaire during 1980-1985. The ages of the patients ranged from one month to 69 years; 90% were less than 15 years of age. The clinical picture was similar to that of the ordinary and modified forms of smallpox. Lymphadenopathy, occurring in the early stage of the illness, was the most important sign differentiating human monkeypox from smallpox and chickenpox. The symptoms, signs, and the course of the disease in patients who had been vaccinated against smallpox differed significantly from those in unvaccinated subjects. Pleomorphism and "cropping" similar to that in chickenpox occurred in 31% of vaccinated and 18% of unvaccinated patients. The prognosis depended largely on the presence of severe complications. No deaths occurred among vaccinated patients. In unvaccinated patients the crude case-fatality rate was 11% but was higher among the youngest children (15%).

Adolescent↗

PubMed1986

Four generations of probable person-to-person transmission of human monkeypox.

This paper examines an outbreak of five cases of human monkeypox which occurred in children belonging to two families living in the West Kasai region of Zaire during May-July 1983. Epidemiologic investigations suggest that the first case was infected from an animal source, possibly a monkey, and that each of the other four cases was infected from a previous human case. Three of these cases of presumed person-to-person transmission occurred in close household contacts. The other case infection occurred either by casual contact within the hospital compound, or possibly because of infection due to use of the same syringe for injections. Human monkeypox is the most important orthopoxvirus infection in the post-smallpox eradication period. The disease is a zoonosis and person-to-person transmission is rather difficult. Thus, this episode is a rare event and special analysis of the circumstances is discussed. However, it supports the necessity to carry out surveillance and research on this disease as recently reported by Arita et al.

Animals↗

PubMed1998

Re-emergence of monkeypox in Africa: a review of the past six years.

Human monkeypox was first identified in 1970 in the Democratic Republic of the Congo. Extensive studies of this zoonotic infection in the 1970s and 1980s indicated a largely sporadic disease with a minority of cases resulting from person-to-person transmission, rarely beyond two generations. In August 1996, an unusually large outbreak of human monkeypox was reported, and cases continued through 1997 with peak incidence in August 1996, March 1997 and August 1997. Preliminary results from the field investigations in 1997 suggest a new epidemiological pattern where a majority of secondary cases result from person-to-person transmission, and a clinically milder disease. But there is preliminary laboratory evidence of a simultaneous outbreak of varicella in the same geographic region which will undoubtedly modify these preliminary results. Since smallpox was eradicated and vaccinia vaccination terminated in this region, the population of susceptible individuals has grown. The use of vaccination to protect the population at risk, however, must take into account HIV prevalence and the risk of generalized vaccinia when using vaccinia vaccine in populations where HIV is known to be present.

Africa↗

PubMed2004

The role of the obstetrician-gynecologist in emerging infectious diseases: monkeypox and pregnancy.

Early in June 2003, the Centers for Disease Control and Prevention (CDC) announced yet another unique infectious disease outbreak, the first evidence of community-acquired monkeypox in the United States. By July 8, 2003, a total of 71 cases had been reported to CDC from 6 states. When emerging infectious diseases are reported in the United States, particularly when these reports receive widespread media attention, obstetrician-gynecologists may be called upon to rapidly respond to queries from their patients and to address certain infectious disease risks within their clinical practices. In addition, obstetrician-gynecologists may have specific concerns about the implications for an infectious disease outbreak, such as monkeypox, for pregnant women. Therefore, it is important that obstetrician-gynecologists know how to gather up-to-date and accurate information about infectious disease outbreaks and that they be familiar with the public health response system for responding to such outbreaks.

Communicable Diseases, Emerging↗